Citric

Citric acid
acid cycle
cycle // TCA
TCA
cycle
cycle
 Citric acid cycle
• Krebs cycle,tricarboxylic acid.
• A series of reactions in mitochondria  oxidize
acetyl Co-A  reduced coenzymes 
reoxidation in respiratory chain
• Functions:
-The final common pathway for aerobic
oxidation of carbohydrate, lipid, protein
-A central role :
1. gluconeogenesis
2. lipogenesis
3. interconversion of amino acids
Citric acid cycle
 Citric acid cycle
• Started with condensation of acetyl coA
with oxaloacetate to form citrate two
molecules of CO2 released and
oxaloacetate regenerated
• Oxaloacetate  catalytic role
• Enzymes: citrate synthase, aconitase,
isocitrate D-ase,  ketoglutarate D-ase
complex, succinate thiokinase, succinate D-
ase, fumarase and malate D-ase
 Citric acid cycle

• Step 1: Acetyl CoA + Oxaloacetate

---Isocitrate
• Acetyl coA + Oxaloacetate + H2O Citrate +
coA + H+.. .(Enzyme : citrate synthase)
• Citrate ↔ Cis aconitate + H2O
• Cis aconitate + H2O ↔ Isositrate
(Enzyme : aconitase)
• Step 2: Isocitrate ---- Succinate

• Isocitrate + NAD+ ↔ αKetoglutarate + CO2 +

NADH..(enzym: Isocitrate D-ase)

• α-Ketoglutarate + NAD+ + CoA ↔ Succinyl coA +

CO2+NADH..(enzym: Succinyl D-ase complex)

• Succinyl coA + Pi + GDP ↔ Succinate + GTP + coA..

(enzym: Succinate Thiokinase)
• Step 3: Succinate ---- Oxaloacetate

• Succinate + FAD ↔ Fumarate + FADH2..

(enzym: succinate D-ase)

• Fumarate + H2O ↔ Malate..(enzym:

Fumarase)

• Malate + NAD+ ↔ Oxaloacetate + NADH +

H+..(enzym: malate D-ase)
 Citric acid cycle
• Result of oxidations: 3 NADH and FADH2
in one turn of cycle
• 1 ATP or GTP formed by substrate level
phosphorylation
• B vitamins involved:
- riboflavin
- niacin
- thiamin
- pantothenic acid
• Riboflavin
to form FAD cofactor in the α-ketoglutarat deh.
Complex & Succinate deh.
• Niacin
to form NADcoenzyme for isocitrate deh.,α-
ketoglutarat deh.,malate deh.
• Thiamin
Thiamin diphosphate coenzyme for
decarboxylation in the α-ketoglutarat deh.
• Panthothenic acid  as part of coA, cofactor
attached to active carboxylic acid residues
(acetyl coA, Succinyl coA)
 Roles in metabolism
• Amphibolic  oxidative and synthesis
processes
1. Gluconeogenesis: all intermediates
potentially glucogenic (give rise to OA 
production of glucose)
• Substrates for gluconeogenesis:
- lactate
- glycerol
- glucogenic amino acids
- propionate
 Roles in metabolism
2. Transamination by aminotransferase:
a source of carbon skeletons for synthesis of
some amino acids  reversible  form some
intermediates from these amino acids:
-aspartate + pyruvate  OA + alanine
-glutamate + pyruvate   keto glut + alanine
3. Acetyl coA is the major building block for
long chain fatty acid synthesis
 Citric Acid Regulating
• Depends on : NAD+,FAD, ADP
• Key enzimes :
Citrate synthase
isocitrate dehydrogenase,
α ketoglutarat dehydrogenase